The goal of this research is to understand gene function, especially in relationship to chromosome structure. Areas of investigation include position-effect variegation and polytene chromosome structure in Drosophila. Also, an attempt will be made to further extend a novel genetic method for the isolation and analysis of genes from higher eukaryotes. This method will be used to identify control sites in a particular "housekeeping" gene. Specific questions asked by the proposal include: (1) What is the molecular basis for position-effect variegation and for clonal inheritance during development? (2) Why do position effects occur? (3) Are neighboring loci affected by an abundantly transcribed puff? (4) What is the function of the RNA from an apparently non-coding puff site? (5) How does a Drosophila housekeeping gene function in yeast? and (6) Can gene selection by yeast transformation be applied generally to multicellular organisms? Molecular biological, genetical, cytological and biochemical techniques will be applied in these analyses. Polytene chromosome methods and gene cloning procedures will be most emphasized for achieving the objectives, although Drosphila and yeast genetic manipulation, enzymology and protein analysis will also be important.